Xiaoqiang Hu , Chuncao He , Lijun Zhang , Yunheng Zhang , Liangjing Chen , Chuan Sun , Jun Wei , Lei Yang , Xiaohua Tan , Jun Yang , Yan Zhang
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引用次数: 0
Abstract
Stem cell-derived exosomes (SC-Exos) have been shown to protect cells from chemical-induced deoxyribonucleic acid (DNA) damage. However, there has been no systematic comparison of the efficacy of exosomes against different types of DNA damage. Therefore, in this study, we assessed the protective effect of exosomes derived from human embryonic stem cell-induced mesenchymal stem cells (hESC-MSC-Exos) on two types of DNA damage, namely, intra-/inter-strand crosslinks and DNA double-strand breaks induced by cisplatin (Pt) and bleomycin (BLM), respectively, in HeLa cells. The alkaline comet assay demonstrated that hESC-MSC-Exos effectively inhibited Pt- and BLM-induced DNA damage in a dose-dependent manner. When the concentration of hESC-MSC-Exos reaches 2.0 × 106 and 4.0 × 106 particles/mL in Pt- and BLM-treated groups, respectively, there was a significant decrease in tail DNA percentage (Pt: 20.80 ± 1.61 vs 9.40 ± 1.14, p < 0.01; BLM: 21.80 ± 1.31 vs 6.70 ± 0.60, p < 0.01), tail moment (Pt: 10.00 ± 1.21 vs 2.08 ± 0.51, p < 0.01; BLM: 12.00 ± 0.81 vs 2.00 ± 0.21, p < 0.01), and olive tail moment (Pt: 6.01 ± 0.55 vs 2.09 ± 0.25, p < 0.01; BLM: 6.03 ± 0.37 vs 1.53 ± 0.13, p < 0.01). Phospho-histone H2AX (γH2AX) immunofluorescence and western blotting showed an over 50 % decrease in γH2AX expression when the cells were pretreated with hESC-MSC-Exos. As reactive oxygen species (ROS) are important mediators of Pt- and BLM-induced DNA damage, dichloro-dihydro-fluorescein diacetate staining indicated that hESC-MSC-Exos inhibited the increase in intracellular ROS in drug-treated cells. In conclusion, our findings suggest that hESC-MSC-Exos can protect cells from the two types of DNA-damaging drugs and that reduced intracellular ROS is involved in this effect.
干细胞衍生的外泌体(SC-Exos)已被证明可以保护细胞免受化学诱导的脱氧核糖核酸(DNA)损伤。然而,目前还没有系统比较外泌体对不同类型DNA损伤的疗效。因此,在本研究中,我们评估了来源于人类胚胎干细胞诱导的间充质干细胞(hESC-MSC-Exos)的外泌体对HeLa细胞中两种类型的DNA损伤的保护作用,即分别由顺铂(Pt)和博来霉素(BLM)诱导的链内/链间交联和DNA双链断裂。碱性彗星试验表明,hESC-MSC-Exos以剂量依赖的方式有效抑制Pt和BLM诱导的DNA损伤。当Pt-和BLM处理组的hESC-MSC-Exos浓度分别达到2.0×106和4.0×106粒子/mL时,尾部DNA百分比显著降低(Pt:28.0±1.61 vs 9.40±1.14,p<;0.01;BLM:21.80±1.31 vs 6.70±0.60,p<;0.01),尾力矩(Pt:10.00±1.21 vs 2.08±0.51,p<;0.01;BLM:12.00±0.81 vs 2.00±0.21,p&lgt;0.01),和橄榄尾力矩(Pt:6.01±0.55vs2.09±0.25,p<;0.01;BLM:6.03±0.37vs1.53±0.13,p&lgt;0.01)。由于活性氧(ROS)是Pt-和BLM诱导的DNA损伤的重要介质,二氯二氢荧光素双乙酸酯染色表明hESC-MSC-Exos抑制了药物处理细胞中细胞内ROS的增加。总之,我们的研究结果表明,hESC-MSC-Exos可以保护细胞免受两种类型的DNA损伤药物的影响,并且减少的细胞内ROS参与了这种作用。
期刊介绍:
Mutation Research - Genetic Toxicology and Environmental Mutagenesis (MRGTEM) publishes papers advancing knowledge in the field of genetic toxicology. Papers are welcomed in the following areas:
New developments in genotoxicity testing of chemical agents (e.g. improvements in methodology of assay systems and interpretation of results).
Alternatives to and refinement of the use of animals in genotoxicity testing.
Nano-genotoxicology, the study of genotoxicity hazards and risks related to novel man-made nanomaterials.
Studies of epigenetic changes in relation to genotoxic effects.
The use of structure-activity relationships in predicting genotoxic effects.
The isolation and chemical characterization of novel environmental mutagens.
The measurement of genotoxic effects in human populations, when accompanied by quantitative measurements of environmental or occupational exposures.
The application of novel technologies for assessing the hazard and risks associated with genotoxic substances (e.g. OMICS or other high-throughput approaches to genotoxicity testing).
MRGTEM is now accepting submissions for a new section of the journal: Current Topics in Genotoxicity Testing, that will be dedicated to the discussion of current issues relating to design, interpretation and strategic use of genotoxicity tests. This section is envisaged to include discussions relating to the development of new international testing guidelines, but also to wider topics in the field. The evaluation of contrasting or opposing viewpoints is welcomed as long as the presentation is in accordance with the journal''s aims, scope, and policies.